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Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus.

Many patients who have type 2 diabetes mellitus (DM) require several different medications. Although these agents can substantially reduce diabetes-related morbidity and mortality, the extent of treatment benefits may be limited by a lack of treatment adherence. Unfortunately, little information is available on treatment adherence in patients with type 2 DM. Available data indicate substantial opportunity for improving clinical outcomes through improved treatment adherence. Factors that appear to influence adherence include the patient's comprehension of the treatment regimen and its benefits, adverse effects, medication costs, and regimen complexity, as well as the patient's emotional well-being. Outcomes research emphasizes the importance of effective patient-provider communication in overcoming some of the barriers to adherence. This article offers specific suggestions for improving adherence in patients with type 2 DM seen in general clinical practice.

Depression↗

Cost-effective designs for linkage disequilibrium mapping of complex traits.

The current development of densely spaced collections of single nucleotide polymorphisms (SNPs) will lead to genomewide association studies for a wide range of diseases in many different populations. Determinations of the appropriate number of SNPs to genotype involve a balancing of power and cost. Several variables are important in these determinations. We show that there are different combinations of sample size and marker density that can be expected to achieve the same power. Within certain bounds, investigators can choose between designs with more subjects and fewer markers or those with more markers and fewer subjects. Which designs are more cost-effective depends on the cost of phenotyping versus the cost of genotyping. We show that, under the assumption of a set cost for genotyping, one can calculate a "threshold cost" for phenotyping; when phenotyping costs per subject are less than this threshold, designs with more subjects will be more cost-effective than designs with more markers. This framework for determining a cost-effective study will aid in the planning of studies, especially if there are choices to be made with respect to phenotyping methods or study populations.

Chromosome Mapping↗

[The Relative Complexity Index beta: value of each parameter].

The French health policy PMSI project (Program for a Medical Information System) is mainly aimed at development of cost analysis based on diagnosis related groups. An indicator of the relative costs of anaesthetics, the relative complexity index (ICR beta), was defined as the result of a computation of different indexes of surgical and anaesthetic procedures such as duration, patients ASA status, degree of emergency, stay in the recovery room. The aims of this study were 1) to analyze relative part of each index in ICR beta value and in ICR beta variance and 2) to assess the value of ICR beta as a cost or a complexity index. The study included 14,435 anaesthetics analyzed with the Dunn and Clarks multiple linear regression. Mean ICR beta was 267.28. The duration of the procedure accounted for 46% of the ICR beta value and surgery for 25%. The anaesthesia and the recovery accounted for 15% of the ICR beta value, but only for 0.0341 and 0.0347 respectively of the ICR beta variance. The product of the surgical procedure index by the ASA status index accounted for 0.259 of the ICR beta variance and the duration index for 0.650. The comparison of homogeneous groups with regard to the surgical procedure shows that intravenous anaesthesia accounts for 12.4% of the ICR beta value, inhalational anaesthesia for 13.84%, but exceeds 15% for regional anaesthesia (44.5% for caudal anaesthesia). For appendectomies (n = 114) duration index is still an important parameter in ICR beta variance (delta R2 = 0.354) but equivalent to the emergency index (delta R2 = 0.363).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Genotypic resistance tests in the management of the HIV-infected patient at virological failure.

Witness for the prosecution: The IAS-USA and Euro-Resistance Group HIV guidelines recommend the use of resistance testing for all patients experiencing treatment failure for whom therapy change is being considered. However, these assays suffer from several limitations (problems in sensitivity, specificity, complexity of interpretation, cost) and the results of the prospective studies evaluating genotype-guided treatment in HIV patients failing antiretroviral treatment are inconclusive and partially contrasting (virological benefit is short-term). On this basis, incorporating genotypic resistance assays into the clinical management of HIV patients experiencing first treatment failure is not a sufficiently evidence-based practice. Witness for the defence: Highly active antiretroviral therapy (HAART) has markedly improved the prognosis of HIV-infected patients by controlling HIV replication. However, HAART fails to control HIV replication in an increasing number of patients as a result of a complex array of causes. There is now substantial evidence that the emergence of drug resistance is a leading cause (as well as consequence) of antiretroviral therapy failure. Moreover, HIV drug resistance can be transmitted and this can favour initial treatment failure. Several retrospective and prospective studies have indicated that both genotypic and phenotypic HIV-1 drug resistance testing results are associated with, or predictive of, the virological outcome. As a consequence, international guidelines have soundly recommended the use of resistance testing to guide treatment choices after virological failure. The rationale and advantages of using such testing after first virological failure will be discussed.

Anti-HIV Agents↗

Cost/benefit analysis of pharmacologic hemostasis.

BACKGROUND: Surgical bleeding with possible associated coagulopathies is a major source of morbidity and mortality. More than 27% of patients receive unnecessary blood or blood-product transfusions during cardiac operations. Analysis of the cost-benefit of pharmacologic hemostasis can be accomplished by relating all the components of cost, which include both direct and indirect costs to both direct and indirect benefits to the patient. METHODS: A significant reduction in transfusion requirements can be achieved by the systematic application of a clinical algorithm. An alternative is to use drugs that enhance hemostasis. Four such drugs commonly used are desmopressin acetate, tranexamic acid, epsilon-aminocaproic acid, and aprotinin. All these agents have been shown to successfully reduce bleeding and the need for transfusion. It appears that the order of efficacy (greatest to least) is aprotinin, tranexamic acid, epsilon-aminocaproic acid, and desmopressin acetate. RESULTS: Cost/benefit analysis associated with the use of these agents is complex. The direct costs of these drug treatments can be balanced against the costs related to blood and blood-product administration. Using epsilon-aminocaproic acid, blood used is valued at $30, whereas the drug treatment cost is less than $2. Aprotinin use results in costs of more than $500, with the drug costing $900. CONCLUSIONS: Improved hemostasis should also result in indirect cost savings from reduced operating room time, reduced intensive care unit and hospital stay, and the avoidance of reoperation for bleeding.

Aminocaproic Acid↗

Minimax regret analysis for municipal solid waste management: an interval-stochastic programming approach.

In this study, an interval minimax regret programming (IMMRP) method is developed for the planning of municipal solid waste (MSW) management under uncertainty. It improves on the existing interval programming and minimax regret analysis methods by allowing uncertainties presented as both intervals and random variables to be effectively communicated into the optimization process. The IMMRP can account for economic consequences under all possible scenarios without any assumption on their probabilities. The developed method is applied to a case study of long-term MSW management planning under uncertainty. Multiple scenarios associated with different cost and risk levels are analyzed. Reasonable solutions are generated, demonstrating complex tradeoffs among system cost, regret level, and system-failure risk. The method can also facilitate examination of the difference between the cost incurred with identified strategy and the least cost under an ideal condition. The results can help determine desired plans and policies for waste management under a variety of uncertainties.

Costs and Cost Analysis↗

Topical corticosteroids for atopic eczema: clinical and cost effectiveness of once-daily vs. more frequent use.

BACKGROUND: Topical corticosteroids remain the mainstay of treatment for atopic eczema, yet there is uncertainty over the frequency of their use in terms of clinical and cost effectiveness. OBJECTIVES: To assess the clinical and cost effectiveness of once-daily vs. more frequent use of same-potency topical corticosteroids in atopic eczema. METHODS: A systematic review of the clinical and cost-effectiveness literature was undertaken, together with a cost-minimization analysis. RESULTS: The review identified a sparse literature, comprising one previous systematic review and 10 randomized controlled trials (RCTs). No published cost-effectiveness studies were identified. RCTs were focused on potent topical corticosteroids (eight RCTs), with no trials (RCTs/controlled clinical trials) identified on mild potency products. There was broad heterogeneity in trial methods, and therefore we considered outcomes according to: (i) at least a good response or 50% improvement, and (ii) eczema rated as cleared or controlled. Studies found little difference between once-daily and more frequent use of topical corticosteroids. The literature on moderately potent and potent corticosteroids offered no basis for favouring once-daily or more frequent use, although some significant differences favouring twice-daily treatment were identified. One RCT on very potent products favoured three times daily use on the basis of clinical response, but reported no difference in the numbers with at least a good response. Given the similar outcomes seen in clinical effectiveness a cost-minimization approach was adopted to consider cost effectiveness, in order to identify the least-cost option. However, cost-minimization analysis proved complex due to wide variations in product price, with the relative cost of product comparisons by frequency proving the most important factor in determining the least-cost alternative. CONCLUSIONS: This review has not identified any clear differences in outcomes between once-daily and more frequent application of topical corticosteroids. We would encourage prescribing clinicians to consider the once-daily use of topical corticosteroids when making treatment decisions for patients with atopic eczema. However, we find that the literature on clinical effectiveness is limited and a broader understanding of compliance and phobia associated with topical steroids is needed to inform on this issue.

Administration, Cutaneous↗

Outsourcing and benchmarking in a rural public hospital: does economic theory provide the complete answer?

INTRODUCTION: The ideology and pronouncements of the Australian Government in introducing 'competitive neutrality' to the public sector has improved efficiency and resource usage. In the health sector, the Human Services Department directed that non-clinical and clinical areas be market tested through benchmarking services against the private sector, with the possibility of outsourcing. These services included car parking, computing, laundry, engineering, cleaning, catering, medical imaging (radiology), pathology, pharmacy, allied health and general practice. Managers, when they choose between outsourcing, and internal servicing and production, would thus ideally base their decision on economic principles. Williamson's transaction cost theory studies the governance mechanisms that can be used to achieve economic efficiency and proposes that the optimal organisation structure is that which minimises transaction costs or the costs of exchange. Williamson proposes that four variables will affect such costs, namely: (i) frequency of exchange; (ii) asset specificity; (iii) environmental uncertainty; and (iv) threat of opportunism. This paper provides evidence from a rural public hospital and examines whether Williamson's transaction cost theory is applicable. METHOD: Case study research operates within the interpretivism paradigm and is used in this research to uncover why the outsourcing decision was made. Such research aims to study real-life experiences by examining the way people think and act and, in contrast to positivism, allows the interviewer to participate to better understand the details and features of the experiences. In the present research, individual interviews were conducted with managers of the hospital and owners and staff of the vendor organisations using semi- and unstructured questions to ascertain the extent of, and processes used in, outsourcing specific functional areas, and areas that were not outsourced. RESULTS: Pathology, radiology, dental technician services and lawn mowing were outsourced while food services was retained internally. The outsourcing of radiology was due to the hospital being unable (or unwilling) to finance new equipment and the problematical relationship between the existing radiologists, and hospital management and staff. Outsourcing resulted in increased staff morale, upgraded capital equipment and improved services. The outsourcing of pathology and dental technical services aimed to increase labour flexibility, thereby decreasing costs. Additional drivers in pathology were the changing nature of the funding arrangements rendering it profitable for the private sector to move into the provision of pathology and the increasing power of the medical scientists' union. The outsourcing of lawn mowing was simply to reduce costs. Food services was not outsourced because there was a lack of evidence that costs could be reduced. In addition, the existing relationships with food services staff were regarded as important because they had previously made immense changes to work practices, reduced staff numbers and decreased costs. CONCLUSION: Transaction costs are important when analysing how managers make the outsourcing decision, but the evidence from this case is that not all transaction costs are included in the decision, and that such costs are more complex than can be included in the type of analysis often undertaken by decision-makers. Taking into account Williamson's variables, the research shows that the outsourcing of services did not comply solely with the levels of transaction frequency or the requirement of asset specificity. In addition, opportunistic behaviour was evident on the part of all parties and was used in some cases as a reason for outsourcing, and in others to sway the decision to the manager's predisposed choice. A variety of arrangements were used to reduce environmental uncertainty, such as the transfer of staff to the contractor and the use of long-term contracts. Indeed the case shows that relationships between the hospital, its staff and the vendor are an important consideration that may not always be factored into an analysis that relies solely on transaction costs.

Journal Article↗

Low-dose dapsone prophylaxis of Pneumocystis carinii pneumonia in AIDS and AIDS-related complex.

The efficacy, toxicity and cost of orally administered dapsone (50-100 mg/day) for prophylaxis of Pneumocystis carinii pneumonia (PCP) were evaluated in 30 patients with AIDS or AIDS-related complex (ARC). Six patients received primary and 24 secondary prophylaxis. Ten patients received a maximum dose of 100 mg/day and 20 a maximum of 50 mg/day for a median duration of 19 weeks; 22 of the 30 patients continue to receive prophylaxis as of May 1989. Four patients have died, none of pneumocystis infection. One patient with AIDS suffered a mild relapse while receiving 50 mg/day. Hematologic toxicity was mild and could not be definitively attributed to dapsone therapy; rash due to dapsone was documented in two patients. A review of 33 patients at our institution with a history of PCP who received no prophylaxis demonstrated seven relapses, three of which were fatal. Cost analysis revealed a significant advantage for oral dapsone over aerosolized pentamidine.

AIDS-Related Complex↗

Transverse low-field RF coils in MRI.

Imaging at low fields imposes a number of nonstandard requirements on the RF coil. At low fields, coil losses are dominant over patient losses. This means that even more stress is put on the quality factor Q. Furthermore, the low frequency also implies a high inductance L and/or a high capacitance C product. Just increasing the capacitance C results in a difficult optimal matching to the preamplifier as well as increased costs and higher complexity of the resonator construction. Coils with a high quality factor Q and a high inductance are thus required at low fields. Birdcage coils possess a number of advantages over saddle and solenoidal coils. However, the currently used birdcages have inherently low inductances limited by the size of the coil. The problem can be solved by a novel design in which the strip configuration for inductors is abandoned and the inductors are realized as a certain number of turns. The Q factor can be further improved by using Litz wire. Three novel transverse RF coils with high inductances are presented and compared with each other as well as to the standard coils. Both linear and quadrature modes are discussed.

Algorithms↗

Environmental management of small-scale and artisanal mining: the Portovelo-Zaruma goldmining area, southern Ecuador.

This paper considers technical measures and policy initiatives needed to improve environmental management in the Portovelo-Zaruma mining district of southern Ecuador. In this area, gold is mined by a large number of small-scale and artisanal operators, and discharges of cyanide and metal-laden tailings have had a severe impact on the shared Ecuadorian-Peruvian Puyango river system. It is shown to be technically possible to confine mining waste and tailings at a reasonable cost. However, the complex topography of the mining district forces tailings management to be communal, where all operators are connected to one central tailings impoundment. This, in turn, implies two things: (i) that a large number of operators must agree to pool resources to bring such a facility into reality; and (ii) that miners must move away from rudimentary operations that survive on a day-to-day basis, towards bigger, mechanized and longer-term sustainable operations that are based on proven ore reserves. It is deemed unlikely that existing environmental regulations and the provision of technical solutions will be sufficient to resolve the environmental problems. Important impediments relate to the limited financial resources available to each individual miner and the problems of pooling these resources, and to the fact that the main impacts of pollution are suffered downstream of the mining district and, hence, do not affect the miners themselves. Three policy measures are therefore suggested. First, the enforcement of existing regulations must be improved, and this may be achieved by the strengthening of the central authority charged with supervision and control of mining activities. Second, local government involvement and local public participation in environmental management needs to be promoted. Third, a clear policy should be defined which promotes the reorganisation of small operations into larger units that are strong enough to sustain rational exploration and environmental obligations. The case study suggests that mining policy in lesser-developed countries should develop to enable small-scale and artisanal miners to form entities that are of a sufficiently large scale to allow adequate and cost-effective environmental protection.

Cost-Benefit Analysis↗

Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease.

BACKGROUND: Several studies have suggested that clinical indices of disease activity in inflammatory bowel disease (IBD) do not adequately reflect the degree of inflammation in most such patients. Faecal excretion of indium-111-labelled neutrophilic granulocytes has been suggested as the gold standard of disease activity, but its complexity and high cost and the exposure of patients to ionizing irradiation have limited the use of this technique. The aim of this study was to investigate the correlation between the faecal excretion of the granulocyte marker protein calprotectin and that of 111In-labelled granulocytes. METHODS: Calprotectin in stool extracts from 19 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 9 presumably healthy controls was assessed with a simple enzyme-linked immunosorbent assay. Simultaneously, the faecal excretion of autologous 111In-labelled granulocytes was measured. RESULTS: There was a strong correlation between the average daily excretion of calprotectin and that of the total 3-day excretion of 111In-labelled granulocytes (r = 0.87, P < 0.0001). Furthermore, the concentration of calprotectin, assessed in a small stool sample on day 1, also correlated well with the excretion 111In-labelled granulocytes (r = 0.80, P < 0.0001). CONCLUSION: The results suggest that faecal calprotectin reflects the granulocyte migration through the gut wall in patients with IBD and hence might serve as a simple, inexpensive alternative to the indium-111 technique.

Adult↗

Determinants of 30-day adverse events following saphenous vein graft intervention with and without a distal occlusion embolic protection device.

Distal balloon occlusion was approved as a means of embolic protection during saphenous vein graft intervention based on its ability to decrease major adverse clinical events (MACEs) by 42% in the 801-patient Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial. However, the cost and technical complexity of this device have limited its widespread use and prompted some to avoid its use in cases that appear at "low risk" for complications. If predictors of MACEs and their potential decrease by distal balloon occlusion could be identified, this would have important clinical implications in this challenging population. We therefore used standard demographic and angiographic variables and 2 new angiographic markers (extent of graft degeneration and estimated volume of plaque in the target lesion) to construct multivariable logistic regression models of 30-day of MACEs in the SAFER trial. Independent correlates of increased 30-day MACEs were more extensive vein graft degeneration (p = 0.0001) and bulkier lesions (larger estimated plaque volume, p = 0.0005). Use of a distal balloon occlusion device was independently predictive of lower 30-day rates of MACE (p = 0.01), with uniform benefit across risk strata (no significant interaction between device use and independent angiographic risk factors). Thus, the risk of 30-day MACEs after percutaneous intervention in aortocoronary saphenous vein grafts is increased in more diffusely diseased grafts and in bulkier lesions, but a significant benefit of the GuardWire was seen across all levels of MACE risk rather than just those perceived to be at highest risk.

Aged↗

Immunoglobulin specificity of TG19318: a novel synthetic ligand for antibody affinity purification.

A synthetic ligand [TG19318], able to mimic protein A in the recognition of the immunoglobulin Fc portion, has been previously identified in our laboratory through the synthesis and screening of multimeric combinatorial peptide libraries. In this study we have fully characterized its applicability in affinity chromatography for the downstream processing of antibodies, examining the specificity and selectivity for polyclonal and monoclonal immunoglobulins derived from different sources. Ligand specificity was broader than protein A, since IgG deriving from human, cow, horse, pig, mouse, rat, rabbit, goat and sheep sera, IgY obtained from egg yolk, and IgM, IgA and IgE were efficiently purified on TG19318 affinity columns. Adsorbed antibodies were conveniently eluted by a buffer change to 0.1 M acetic acid or 0.1 M sodium bicarbonate pH 9, with full retention of immunological properties. Monoclonal antibodies deriving from cell culture supernatants or ascitic fluids were also conveniently purified on TG19318 affinity columns, even from very diluted samples. The affinity constant for the TG19318-IgG interaction was 0.3 microM, as determined by optical biosensor measurements. Under optimized conditions, antibody purity after affinity purification was close to 95%, as determined by densitometric scanning of SDS-PAGE gels of purified fractions, and maximal column capacity reached 25 mg Ig/ml support. In vivo toxicity studies in mice indicated a ligand oral toxicity greater than 2000 mg kg-1 while intravenous toxicity was close to 150 mg kg-1. Validation of antibody affinity purification processes for therapeutic use, a very complex, laborious and costly procedure, is going to be simplified by the use of TG19318, which could reduce considerably the presence of biological contaminants in the purified preparation, a very recurrent problem when using recombinant or extractive biomolecules as affinity ligands.

Animals↗

Multistation multiparameter flow cytometry: a critical review and rationale.

The capacity for fluorescence excitation by beams of different wavelengths at separate points along the sample stream, and the capacity for computer analysis of multiparameter data thus obtained, are now available in flow cytometer/sorter systems from commercial producers. It is now readily apparent to most experienced users of flow cytometers that such multiparameter analysis offers the most convenient solution to the problem of characterizing subpopulations of cells within a mixed population. The use of multiple beams facilitates resolution of fluorescence signals from several probes within or upon a single cell and widens the range of analytical alternatives available to experimenters. This critical review discusses the history of the instrumentation, the parameters now measurable and the probes used for their measurement, and the methods for data analysis. Required sensitivity and precision are discussed, leading to the conclusion that many of the advantages of multistation, multiparameter flow cytometry can be made available in less complex and less costly instruments using less powerful sources and less elaborate computer hardware than are presently incorporated in commercial apparatus.

Antigens, Surface↗

Improved Shinnar-Le Roux algorithm.

Selective excitation pulses are widely used in magnetic resonance imaging in order to excite predetermined slices of the body under examination. Such pulses are optimally designed by means of the Shinnar-Le Roux algorithm. In this paper, we show that under minimal assumptions, the complexity and computing cost of the original Shinnar-Le Roux algorithm can be drastically reduced. We further propose an improved version of the algorithm, involving only real quantities, which is both easier to implement and faster to execute, so it is suitable for implementation at the hardware level, in the context of a real-time fully digital magnetic resonance transceiver.

Algorithms↗

Rapid assessment of regional cerebral metabolic abnormalities in single subjects with quantitative and nonquantitative [18F]FDG PET: A clinical validation of statistical parametric mapping.

The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion studies.

Adolescent↗

[Magnetic resonance imaging of the hand in rheumatoid arthritis. New scientific insights and practical application].

Magnetic resonance imaging (MRI) is a sensitive diagnostic modality for the detection of inflammatory changes in peripheral joints. Nevertheless, the widespread clinical use of MRI in assessing patients with early rheumatoid arthritis is still hampered by the technical complexity and higher cost of MRI compared with conventional radiography. This overview summarizes the results of recent research and gives practical tips on how to perform MRI of the hands. The authors present an MR protocol for hand imaging, discuss the pros and cons of low-field MR scanners, and outline pitfalls and artifacts. The MRI changes associated with rheumatoid arthritis such as synovitis, tenosynovitis, erosions, and bone marrow edema are described including their prognostic significance. The proven facts on the validation and grading of MR changes in rheumatoid arthritis are summarized. Finally, the role of MRI in the differential diagnosis of arthritis is critically discussed.

Arthritis, Rheumatoid↗